反应详情

To the stirred solution of 4-(4-bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid (516 gm, 1.49 mmol) in THF (10 ml) under argon at room temperature is added a solution of 2-tert-butyl-1,3-diisopropylisourea (1.49 g, 7.45 mmol) in THF (1.0 ml). The resulted mixture is refluxed for 6 hours. The reaction mixture is then cooled to room temperature and diluted with ethyl acetate. The organic layer is washed with 10% K2CO3 (20 ml×2) and saturated NaCl (30 ml×3), dried over Na2SO4 and concentrated in vacuum. The residue is dissolved in 30 ml of dichloromethane and the resulting white solid (urea byproduct) is filtered out. The filtrate is concentrated under reduced pressure. The residue is purified by flash column chromatography to provide the desired product.

1. temperatureThe resulted mixture is refluxed for 6 hours
2. washThe organic layer is washed with 10% K2CO3 (20 ml×2) and saturated NaCl (30 ml×3)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated in vacuum
5. dissolutionThe residue is dissolved in 30 ml of dichloromethane
6. filtrationthe resulting white solid (urea byproduct) is filtered out
7. concentrationThe filtrate is concentrated under reduced pressure
8. customThe residue is purified by flash column chromatography